tbuckley/cabot-search huggingface dataset:
Association between sociodemographic factors and diagnosis of advanced prostate cancer in early life.
Authors: Shayan Smani, Madison Novosel, Farah Jeong, Victoria A. Marks, Preston Sprenkle, Michael Leapman
Journal: Journal of Clinical Oncology (2023)

32 Background: A subset of patients are diagnosed with lethal prostate cancer early in life, before PSA screening is typically initiated. To identify opportunities for improved detection we evaluated patient clinical and sociodemographic factors associated with advanced versus localized prostate cancer diagnosis across the age spectrum. Methods: We conducted a retrospective cohort study using the National Cancer Database, identifying patients diagnosed with prostate cancer in 2004-2016. We compared characteristics of patients diagnosed at advanced (cN1 or M1) versus localized (cT1-4N0M0) stage. Using multivariable logistic regression, we evaluated the associations among patient clinical and sociodemographic factors and advanced diagnosis, stratifying patients by age as &lt;55 (before screening is usually initiated), 55-65, 65-75, and &gt;75 years. Results: We identified668,486 patients who met inclusion criteria (mean age at diagnosis=64.6 years), including 33,455 (5.0%) with advanced disease at diagnosis. Uninsured (odds ratio, OR=3.78, 95% confidence interval, CI 3.56-4.02) and Medicaid-insured (OR 2.84, 95% CI 2.70-3.00) versus commercially insured patients were more likely to be diagnosed with advanced disease, however this effect was more pronounced for younger patients. Among patients &lt;55 years, uninsured (OR 4.63, 95% CI 4.08-5.25) and Medicaid (OR 3.59, 95% CI 3.22-3.99) versus commercial insurance were associated with greater odds of advanced cancer at diagnosis. Similarly, residence in the lowest versus highest income quintile (OR 1.21, 95% CI 1.04-1.40) was associated with increased odds of advanced prostate cancer in patients &lt;55 years. Black versus White race was associated with increased odds of advanced prostate cancer at diagnosis later in life (OR 1.15, 95% CI 1.11-1.19), however race was not significantly associated with stage of prostate cancer in those &lt;55 years (p=0.29). Conclusions: Sociodemographic disparities in advanced stages of prostate cancer diagnosis were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early prostate cancer screening by health insurance.
Outcomes by IMDC risk in the COSMIC-313 phase 3 trial evaluating cabozantinib (C) plus nivolumab (N) and ipilimumab (I) in first-line advanced RCC (aRCC) of IMDC intermediate or poor risk.
Authors: Thomas Powles, Robert J. Motzer, Laurence Albiges, Cristina Suárez, Fabio A. B. Schutz, Daniel Yick Chin Heng, Christine Chevreau, Ravindran Kanesvaran, Howard Gurney, Fong Wang, Fabio Mataveli, Yu-Lin Chang, Maximiliano van Kooten Losio, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2023)

605 Background: In COSMIC-313 (NCT03937219), C+N+I significantly improved progression-free survival (PFS) compared with N+I in first-line aRCC of IMDC intermediate or poor risk (Choueiri ESMO 2022). Here, outcomes are analyzed by IMDC risk group. Methods: A total of 855 patients (pts) with clear cell aRCC of IMDC intermediate or poor risk were randomized to receive C 40 mg QD or matched placebo (P), stratified by region and IMDC risk. Both treatment groups received N (3 mg/kg IV Q3W) + I (1 mg/kg IV Q3W) for 4 cycles followed by N (480 mg IV Q4W); N was administered for up to 2 years. The primary endpoint was PFS by blinded independent radiology review (BIRC) per RECIST 1.1 in the first 550 randomized pts (PITT population). The secondary endpoint was overall survival (OS) in all randomized pts; objective response rate (ORR) and safety were additional endpoints. Results: Overall, 75% of pts were IMDC intermediate and 25% were poor risk. Meaningful differences in baseline characteristics for intermediate vs poor risk in the PITT population were observed for KPS ≥90 (67% vs 47%), prior nephrectomy (71% vs 44%), and ≥2 target/non-target lesions per BIRC (68% vs 83%); characteristics were balanced across treatment arms for intermediate risk but some imbalances were seen for poor risk (42% for C+N+I vs 52% for P+N+I had KPS ≥90 and 37% vs 50% had prior nephrectomy). In intermediate risk pts, PFS was improved with C+N+I (HR 0.63, 95% CI 0.47–0.85), and ORR and DCR (PITT population) were numerically higher (Table). For poor risk pts, no difference in PFS and ORR was apparent, but DCR was numerically higher with C+N+I. PD as best response was lower with C+N+I vs P+N+I in both risk groups. Duration of response was not reached (NR) in each treatment group. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 74% with C+N+I vs 42% with P+N+I for intermediate risk and 67% vs 38% for poor risk. TRAEs led to discontinuation of all treatment components in 14% vs 5% for intermediate risk and 5% vs 4% for poor risk. Additional analyses relevant to IMDC risk group will be presented. Conclusions: In COSMIC-313, C+N+I improved PFS vs P+N+I in first-line aRCC of IMDC intermediate or poor risk; subgroup analysis suggested that the benefit was primarily in intermediate risk pts. Follow-up for OS is ongoing. Clinical trial information: NCT03937219 . [Table: see text]
Ga-68 PSMA-11 impacting prostate cancer management in a real-world setting: A pilot experience using the total-body PET/CT scanner.
Authors: Harshad R Kulkarni, Dan Rogers, Kevin Maupin, Todd Faasse, Jens Forsberg, Matt DeLong, Brandon Robert Mancini
Journal: Journal of Clinical Oncology (2023)

62 Background: PET/CT using Ga-68 PSMA-11, which received FDA approval, can detect early biochemical recurrence of prostate cancer at greater sensitivity than conventional imaging, as well as more accurately clinical stage and impact treatment management, particularly vital for high-risk patients. We present our first experience with Ga-68 PSMA-11 PET/CT using the total-body PET/CT scanner (uExplorer). Methods: PET/CT imaging (1-bed acquisition of the entire body for 5 minutes) was performed on the uExplorer scanner 56-65 minutes after administering 150-200 MBq of Ga-68 PSMA-11 (Illucix) in 14 patients with prostate cancer at our clinic. The medical records of these patients were reviewed. Results: Of the 14 patients who underwent Ga-68 PSMA-11 total-body PET/CT, 6 had high risk, 6 had intermediate risk and 2 had low risk cancers. The scan was negative in 1 patient, whereas local recurrence and pelvic lymph nodes could be identified in the other patient with low-risk prostate cancer. The smallest size of the lymph node identified was 2 mm. All patients with intermediate and high-risk cancers had metastatic disease – 2 had metastases to the lymph nodes only. Of the 10 patients with widespread metastases to bones and lymph nodes, 4 had additional visceral metastases – in 3 patients to the lungs and in 1 to the liver. The line of management changed in 10/13 patients with a positive scan – 5 were treated with Lu-177 PSMA radioligand, 4 with chemotherapy and 1 with local irradiation. Conclusions: Our pilot experience is consistent with the clinical value of Ga-68 PSMA-11 PET/CT (Illucix) imaging to better inform patient management, in addition to demonstrating the role of rapid and high-resolution imaging with the total-body PET/CT scanner (uExplorer). With the availability of PSMA PET/CT, it should be considered the new standard of care for men who have prostate cancer for staging or localization of recurrence.
Combined alternating sunitinib and bevacizumab in the management of advanced renal cell carcinoma: A phase I/II trial.
Authors: Shouki Bazarbashi, Ahmed M Alzahrani, Ali H Aljubran, Mahmoud Abdelsatar Elshenawy, Ahmed Mostafa Gad, Fatma Maraiki, Noura Alzannan, Tusneem Elhassan, Ahmed Ali Badran
Journal: Journal of Clinical Oncology (2023)

665 Background: Tyrosine kinase inhibitors remain a corner stone in the management of metastatic clear cell renal cell carcinoma (RCC). The intermittent schedule of sunitinib with 4 weeks on/2 weeks off could result in a rebound angiogenesis and tumor progression in the 2 weeks rest period. We propose the use of bevacizumab to alternate with sunitinib to attain continuous anti-angiogenesis during sunitinib therapy. Methods: This was a phase I/II design. Patients advanced clear cell RCC were recruited. Sunitinib was given as 50 mg daily on 4 weeks on/2 weeks off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. Bevacizumab starting dose was 5 mg/kg and the dose was escalated to 10 mg if no dose limiting toxicity. Primary endpoints were response rate and progression-free survival. Results: Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose limiting toxicity was found on the 5 mg dose level of bevacizumab. One patient achieved complete response and 12 achieved partial response for a response rate of 52%. At a median follow up was 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median progression-free survival was 16.5 months (95% CI 4.1-28.8), and the median overall survival was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity. The commonest grade 3 or 4 toxicity was thrombocytopenia and lymphopenia each occurring at a rate of 32%, followed by hypertension at a rate of 28% followed by fatigue at a rate of 24%. Conclusions: Continuous angiogenesis blockade by adding bevacizumab to sunitinib 4 weeks on and 2 weeks break regimen in advanced RCC produce significant anti-tumor activity with manageable increased toxicity. Clinical trial information: NCT02919371 .
Clinical characteristics and outcomes of trial-ineligible patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving androgen receptor targeted (ART) therapy.
Authors: George Slade Mellgard, Stephen Mccroskery, Zakaria Chakrani, Nathaniel Saffran, Nicole Taylor, Bobby Chi-Hung Liaw, Matt D. Galsky, William K. Oh, Kai Tsao, Vaibhav G. Patel
Journal: Journal of Clinical Oncology (2023)

118 Background: mCRPC pts with significant comorbidities or poor performance status (PS) are often excluded from clinical trials for ART. These cohorts may not be representative of or comparable to real-world pts. We aimed to determine whether (1) baseline characteristics or (2) survival outcomes differed in pts with mCRPC categorized as eligible or ineligible for ART clinical trials. Methods: We screened for pts with mCRPC treated with abiraterone (abi-) or enzalutamide (enza-) at our institution between 2010 and 2021. Baseline characteristics were reviewed at treatment start and ART course recorded. We applied the inclusion/exclusion criteria from clinical trials, COU-AA-301, COU-AA-302, PREVAIL, and AFFIRM, to categorize pts as ineligible or eligible. Fischer’s exact was used to evaluate pt characteristics. Cox proportional hazards model was used to compare survival outcomes. Results: We identified 150 pts with mCRPC who initiated abi- or enza-. 54.7% of pts were deemed trial ineligible. Among pts on abi-, 48 of 86 (55.8%) pts were ineligible. Among those on enza-, 34 of 64 (53.1%) were ineligible. Common reasons for ineligibility included poor PS, radiation during treatment, and trial specific comorbidities. Among ineligible pts, 11% were post-chemotherapy compared to 20.6% of eligible pts (p = .162). Notably, trial ineligible pts were more likely to be non-Hispanic black when compared to trial eligible pts (29.3% vs. 17.6%, p = 0.036). Median OS was 30.2 for ineligible pts and 37.1 for eligible pts p = 0.46). for the ineligible pts and eligible pts respectively and there was no significant difference on univariate or multivariate analyses (HR: 0.84 [0.54, 1.32;]. Conclusions: Pts classified as trial ineligible had comparable survival outcomes when compared to trial eligible pts. Consistent with prior research on systemic racism in clinical trials, ineligible pts were more likely to identify as Black compared to eligible pts. Further research is warranted to confirm safety of ART in ineligible pts and identify strategies for reducing racial disparity gaps in cancer clinical trials.
Diagnosis of prostate cancer using cell-free DNA methylation profiles from expressed prostatic secretions.
Authors: Wenhao Shen, Hang Dong, Haoran Tang, Yue Zhang, Shidong Jia, Yang Luo
Journal: Journal of Clinical Oncology (2023)

389 Background: Urinary and seminal cell-free DNA (cfDNA) have been recognized as promising biomarkers of prostate cancer. DNA methylation signal in tumor is increasingly used as tumor diagnosis and longitudinal monitoring indicator. However, the clinical utility of cfDNA from expressed prostatic secretions (EPS) remains unknown. Methods: The prospective study includes 50 prostate cancer (PC) patients and equivalent benign prostatic hyperplasia (BPH) patients, where EPS samples were collected after the prostatic massage of each patient. Cell-free DNA from EPS was extracted and treated by PredicineEPIC, a liquid biopsy comprehensive DNA methylation assay. The study developed integrated bioinformatic algorithms to profile the genome-wide epigenomic characteristics and investigate tumor-specific methylation patterns. Results: The initial exploratory cohort included 5 PC and 11 BPH cases. PredicineEPIC whole-genome DNA methylation of EPS identified over 300 differentially methylated regions (DMRs). Prostate cancers were distinguished from the BPH group by an unsupervised clustering method, suggesting that the identified DMRs embody the specific profiles of malignant tumors. Additionally, this study detected genome-wide copy number variation burden (CNB) in parallel. A risk model was built for cancer risk assessment based on methylation and CNB characteristics. Conclusions: This study demonstrated the feasibility of methylation profiling of cfDNA in EPS in prostate cancer. This non-invasive liquid biopsy approach could sensitively navigate prostate cancer from benign prostatic hyperplasia, suggesting future direction of methylation-based liquid biopsy in detecting prostate cancer.
A phase II study of rucaparib monotherapy in nonmetastatic, hormone-sensitive prostate cancer (nmHSPC) with “BCRAness” genotype (ROAR).
Authors: Kamal Kant Kant Sahu, Haoran Li, Vinay Mathew Thomas, Mallory Benson, Josiah Hawaks, Julian Brown, Kelli Thorne, Kathy Sherwin, Jackson Cheney, Kenneth M. Boucher, Sumati Gupta, Manish Kohli, Umang Swami, Neeraj Agarwal, Benjamin L. Maughan
Journal: Journal of Clinical Oncology (2023)

364 Background: Prostate cancer (PCa) patients (pts) with DNA repair defects (aka “BRCAness”) generally have more aggressive disease and a worse overall prognosis compared to men without BRCAness (PMID: 33781305). Biochemical recurrence (BCR) develops in almost one-third of men with PCa after treatment with local therapy. We hypothesized that treatment with rucaparib monotherapy in men with systemic treatment naïve high-risk nmHSPC would result in acceptable disease control, allow a delay of androgen deprivation therapy (ADT) and the onset of metastasis. Methods: This is a single-arm, open-label, phase II trial; eligibility criteria: (1) Histologically proven prostate adenocarcinoma, presence of one of the following alterations in (by soft tissue or liquid biopsy): BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FANCA, NBN, PALB2, RAD51C, RAD51D, RAD51, RAD51B, (2) No radiographic evidence of metastatic disease by conventional scans (3) PSA doubling time of ≤10 months. The primary endpoint: PSA progression-free survival (PSA-PFS). Secondary endpoints: safety, the proportion of pts with a PSA 50% response (PSA50), and an undetectable PSA. Results: Seven pts were enrolled in the study with the following pathogenic alterations: ATM (n=3), BRCA2 (n=2), BRCA1 (n=1), BRIP1 (n=1), RAD51(n=1), and received treatment with rucaparib at 600 mg twice daily. A 4-week treatment duration comprised one cycle. The median duration of follow-up was 18 months. A median of 20 cycles (range 4-42) was completed, median PSA-PFS was 35.37 months (95% CI: 0 - 85.11 months). 2/7 patients achieved PSA50; both had nadir PSA as undetectable. Grade ≥ 3 adverse events (AEs) were anemia and rash (in 1 pt each). No dose-limiting toxicities or severe AEs were seen. The study was prematurely terminated in June 2022 after the accrual of 7 pts because next-generation scans (e.g., PSMA-PET) became the standard of care for pts with BCR. Conclusions: Rucaparib demonstrated acceptable toxicity and preliminary efficacy in pts with PCa with BCR. Gene alteration-specific efficacy will be presented in the meeting. Limitations: Small cohort, no comparison arm. Hence results should be interpreted cautiously but generally consistent with larger prospective trials of PARP inhibitors. Clinical trial information: NCT03533946 . [Table: see text]
Novel retroperitoneal neovascularity scoring system in renal cell carcinoma tumor staging.
Authors: Cameron Fateri, Akhil Peta, Thahn-Lan Bui, Nina Kar, Bradley Roth, Sung-Mee Park, Justin Glavis-Bloom, Roozbeh Houshyar, Jaime Landman
Journal: Journal of Clinical Oncology (2023)

620 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer worldwide. While radiologists assess enhancement patterns of renal tumors to predict tumor pathology, to our knowledge, no formal scoring system has been created and validated to assess the level of neovascularity in RCC, despite its critical role in cancer metastases. In this study, we characterized and analyzed the level of angiogenesis in tumor-burdened kidneys and their benign counterparts. We then created and validated a scoring scale for neovascularity that can help predict tumor staging for RCC. Methods: After Institutional Review Board approval, the charts of patients who had undergone surgery for RCC between January 13, 2014 and February 4, 2020 were retrospectively reviewed for inclusion in this study. Inclusion criteria were a diagnosis of RCC, simple/radical nephrectomy, pre-operative contrast enhanced computed tomography (CT) scans, and complete pathology reports. Neovascularity was scored on a scale of 0 to 4 where 0= no neovascularity detected, 1= a single vessel &lt;3mm wide, 2= a single vessel &gt;3mm wide, 3=multiple vessels &lt;3mm wide, and 4=multiple vessels &gt;3mm wide Results: A total of 227 patients were included in the study. The majority of tumor pathology was clear cell carcinoma, regardless of tumor staging. The average neovascularity score was 1.07 for pT1x tumors, 2.83 for pT2x tumors, and 3.04 for pT3x tumors. There was a significant difference in neovascularity score between pT1x and pT2x tumors (p = 0.0046), pT1x and pT3x tumors (p &lt; 0.0001), and benign kidneys and kidneys with RCC (p = &lt;0.0001). Furthermore, we sought to address the ability of the Re-VASC score to predict up-staging or down-staging of clinically staged tumors. Only 5 total tumors were upstaged from cT1 to any pathological stage &gt;1, with an average Re-VASC score of 2.33. There were 24 cases that were down-staged to pT1, with an average Re-VASC score of 1.73. Additionally, we specifically looked at cT3a tumors that were down-staged to p1x. The average Re-VASC scores were 0.82 and 2.11 for pT1a and pT1b tumors respectively. Conclusions: Our novel vascular scoring system for renal cell carcinoma demonstrates significant correlation with RCC pathological tumor staging. In future studies, we would like to further explore the ability of the scoring system to predict clinical up-staging and down-staging, as we had a limited sample size to analyze this function. This scoring system may be utilized as part of a comprehensive radiological assessment of renal tumors, potentially improving tumor characterization and clinical decision making.
Pembrolizumab (Pem) in metastatic castration-resistant prostate cancer (mCRPC): Experience from a comprehensive cancer center.
Authors: Arya Mariam Roy, Bailey Farmer, Vasanthan Muthusamy Kumarasamy, Karan Jatwani, Ellis Glenn Levine, Gurkamal S. Chatta, Dharmesh Gopalakrishnan
Journal: Journal of Clinical Oncology (2023)

113 Background: The prognosis of refractory mCRPC remains poor despite advancements in therapeutic options. KeyNote-199 demonstrated modest activity of Pem in mCRPC with expected safety profile. We present our real-world experience with Pem in mCRPC. Methods: We conducted a retrospective review of mCRPC patients treated with Pem at our institution from 1/1/2017 to 10/1/22. Baseline demographic, clinicopathologic, and genomic characteristics were recorded. PSA and radiographic responses were assessed by the study team, and survival distributions estimated using the Kaplan-Meier method. Results: A total of 39 patients were identified – 97% (37) were White, median age was 71 years, 4% (19/35) had a Gleason Score ≥8; 80% (31) had skeletal and 74% (29) had soft tissue metastases at Pem initiation. Overall, patients were heavily pre-treated (median of 7 prior therapies, range 0-8) - 87% (34) had received taxanes, 82% (32) novel antiandrogens, 23% (9) Ra-223, 21% (8) Sipuleucel-T, and 2% (1) Olaparib. Median duration on Pem was 7 months (range = 1-29). Among the 34 evaluable patients, 2 (6%) achieved CR, 2 (6%) had PR, 5 (15%) had stable disease (SD), and 25 (73%) had progressive disease (PD) on radiographic assessment. PSA reduction ≥ 50% was noted in 7/32 (22%) patients. The 4 patients who had radiographic CR/PR had positive predictive biomarkers – Patient 1: CR – MSI-H, high TMB (17.5/Mb); Patient 2: CR – MSI-indeterminate, germline MSH6 mutation; Patient 3: PR – MSI-H, high TMB (28.8/Mb), germline MSH2 mutation; and Patient 4: PR – MSI-S, high TMB (18.3/Mb), PDL1 TPS 100%, positive neuroendocrine markers. Interestingly, patient 3 was switched to ipilimumab + nivolumab after PD on Pem, and subsequently had a CR. None of the evaluated patients with SD or PD had high MSI, TMB, or PDL1 levels. The median overall survival from Pem initiation was 4.4 months (95% CI 3.0-10.2 months). Three (8%) patients discontinued Pem due to immune-related adverse effects (IRAEs); no treatment-related deaths were reported. The most frequent Gr 3 IRAEs are shown. Conclusions: Single-agent Pem demonstrated modest overall efficacy in mCRPC, restricted only to patients with predictive biomarkers. Given the non-trivial risk of IRAEs, financial toxicity, and potential QoL implications, we suggest using checkpoint inhibitors only in appropriately biomarker-selected patients with mCRPC. [Table: see text]